Penicillin G sodium salt Sandoz powder for solution for injection 1000000 IU bottle No. 100

Instructions Penicillin G sodium salt Sandoz powder for solution for injection 1000000 IU bottle No. 100

Composition

active ingredient: benzylpenicillin sodium;

1 vial contains benzylpenicillin sodium salt 1,000,000 IU.

Dosage form

Powder for solution for injection.

Main physicochemical properties: white or almost white powder.

Pharmacotherapeutic group

Beta-lactam antibiotics. Penicillins sensitive to the action of beta-lactamases. ATX code J01C E01.

Pharmacological properties

Pharmacodynamics.

Penicillin G sodium salt is a water-soluble benzylpenicillin that exerts a bactericidal effect on sensitive microorganisms by inhibiting cell wall biosynthesis through blockade of penicillin-binding proteins.

Resistance Resistance to benzylpenicillin may occur in the following cases:

inactivation of beta-lactamases: benzylpenicillin is sensitive to beta-lactamase and therefore inactive against bacteria that produce beta-lactamase (for example, staphylococci or gonococci);

Decreased affinity of penicillin-binding proteins for benzylpenicillin: Acquired resistance to benzylpenicillin in pneumococci and several other streptococci is due to changes in existing penicillin-binding proteins as a result of mutation. However, the formation of additional penicillin-binding proteins with reduced affinity for benzylpenicillin is the result of resistance in methicillin (oxacillin)-resistant staphylococci;

in gram-negative bacteria, insufficient penetration of penicillin through the outer cell wall may lead to insufficient inhibition of penicillin-binding proteins;

benzylpenicillin can be actively transported out of the cell using efflux pumps;

Benzylpenicillin is partially or completely cross-resistant to other penicillins and cephalosporins.

Checkpoints

Benzylpenicillin testing is performed using a standard dilution series. Results are evaluated based on the control points for benzylpenicillin. The following minimum inhibitory concentrations have been established for susceptible and resistant microbes:

Information on pathogen resistance

Favorable types

Aerobic gram-positive microorganisms: Actinomyces israelii, Corynebacterium diphtheriae, Erysipelothrix rhusiopathiae, Gardnerella vaginalis, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus dysgalactiae subsp. Equisimilis (Group C & G streptococci)

Aerobic gram-negative microorganisms: Borrelia burgdorferi, Eikenella corrodens, Haemophilus influenzae, Neisseria meningitidis.

Anaerobic microorganisms: Clostridium perfringens, Clostridium tetani, Fusobacterium spp., Peptoniphilus spp., Peptostreptococcus spp., Veillonella parvula.

Other microorganisms: Treponema pallidum.

Species in which acquired resistance may be a problem during treatment

Aerobic gram-positive microorganisms: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis.

Aerobic Gram-negative microorganisms: Neisseria gonorrhoeae.

Naturally resistant species

Aerobic gram-positive microorganisms: Enterococcus faecium, Nocardia asteroids.

Aerobic Gram-negative microorganisms: all Enterobacteriaceae species, Moraxella catarrhalis, Pseudomonas aeruginosa.

Anaerobic microorganisms: Bacteroides spp.

Other microorganisms: Chlamydia spp., Chlamydophila spp., Legionella pneumophila, Mycoplasma spp.

Pharmacokinetics.

Absorption

Benzylpenicillin is not acid-stable and is therefore administered parenterally only. Alkaline salts of benzylpenicillin are rapidly and completely absorbed after intramuscular injection. Peak plasma levels of 150-200 IU/ml are reached 15-30 minutes after intramuscular injection of 10 million IU of the drug. After short-term infusions (30 minutes), levels may reach a maximum of 500 IU/ml. Binding to plasma proteins is approximately 55% of the total dose.

Distribution

After administration of high doses of penicillin, therapeutic concentrations are also reached in hard-to-reach tissues such as heart valves, bones and cerebrospinal fluid. Benzylpenicillin crosses the placenta. 10-30% of the maternal plasma concentration is found in the fetal blood. High concentrations are also reached in the amniotic fluid. On the other hand, penetration into breast milk is low. The volume of distribution is about 0.3-0.4 l/kg; in children about 0.75 l/kg. Binding to plasma proteins is about 55%.

Metabolism and excretion

Excretion occurs mainly (50-80%) as unchanged substance via the kidneys (85-95%) and, to a lesser extent, in the active form with bile (about 5%). The plasma half-life is about 30 minutes in adults with healthy kidneys.

Kinetics of special patient groups

Premature and newborn infants: Since renal and hepatic functions in premature infants and newborns are still immature, the serum half-life is approximately 3 hours (or more). Therefore, the interval between doses should be at least 8-12 hours (depending on the degree of organ maturity).

Elderly patients: elimination may be delayed, dosage should be adjusted according to renal function in each individual case.

To increase the interval between doses, the drug can be combined with depot penicillin preparations.

Indication

Infectious diseases caused by penicillin-sensitive microorganisms: sepsis, wound and skin infections, diphtheria (as an adjunct to antitoxin), pneumonia, empyema, erysipeloid, pericarditis, bacterial endocarditis, mediastinitis, peritonitis, meningitis, brain abscesses, arthritis, osteomyelitis, genital tract infections caused by fusobacteria, as well as in specific infections: anthrax; infections caused by clostridia, including tetanus, listeriosis, pasteurellosis; rat-bite fever; fusospirochetosis, actinomycosis; treatment of complications caused by gonorrhea and syphilis, Lyme borreliosis after the first stage of the disease.

Contraindication

Hypersensitivity to beta-lactam antibiotics (penicillins and cephalosporins), the possibility of cross-allergy should be taken into account. Newborns whose mothers have hypersensitivity to penicillin antibiotics. Epilepsy (with intralumbar administration). Severe allergic reactions and bronchial asthma in history.

Interaction with other medicinal products and other types of interactions

Concomitant administration of penicillin is not recommended with bacteriostatic antibiotics, since penicillins only act on proliferating microbes.

Mixed injections or infusions: To avoid undesirable chemical reactions, the administration of mixed injections or infusions or supplements with solutions that contain carbohydrates such as glucose should be avoided.

Combination with other antibiotics is advisable only when a synergistic effect or any additional effect can be expected. The individual components of the therapeutic combination should be administered in full dose (the dose of the more toxic component may be reduced if a synergistic effect is shown). Bactericidal antibiotics used in combination with the drug include isoxazolylpenicillins, for example, flucloxacillin and other narrow-spectrum beta-lactam antibiotics, aminopenicillins, aminoglycosides. They should be administered by slow intravenous injection before the administration of benzylpenicillin. If possible, aminoglycosides should be administered intramuscularly separately.

The possibility of competitive inhibition of the process of excretion from the body should be borne in mind when benzylpenicillin is used simultaneously with anti-inflammatory, antirheumatic and antipyretic agents (indomethacin, phenylbutazone, salicylates in high doses).

Aspirin, probenecid, thiazide diuretics, furosemide, ethacrynic acid increase the half-life of benzylpenicillin, increasing its concentration in blood plasma, which increases the risk of its toxic effects by affecting renal tubular secretion.

Allopurinol increases the risk of developing allergic reactions (skin rashes).

The use of benzylpenicillin may in some cases cause a decrease in the effectiveness of oral contraceptives.

The drug is incompatible with metal ions, especially copper, mercury, zinc and zinc compounds, which may be part of the rubber stoppers of infusion bottles. Substances with oxidizing and reducing properties, alcohol, glycerin, macrogols and other hydroxyl compounds can also inactivate it. In weakly alkaline solutions, the drug is rapidly inactivated by cysteine and other aminothiol compounds. Sympathomimetic amines are also incompatible with benzylpenicillin.

The drug should not be used in dextrose solution. Avoid simultaneous use with chloramphenicol, erythromycin, tetracycline, sulfonamides.

Concomitant use with methotrexate reduces the excretion of the latter and increases the risk of its toxicity. Concomitant use of methotrexate and benzylpenicillin should be avoided if possible. If concomitant use is unavoidable, the dose of methotrexate should be reduced and serum methotrexate levels monitored. Portiben should be monitored for possible additional adverse reactions, including leukopenia, thrombocytopenia and skin suppuration.

When benzylpenicillin is administered simultaneously with anti-inflammatory, antirheumatic or antipyretic drugs (especially indomethacin, phenylbutazone, salicylates in high doses), it should be noted that excretion is competitively inhibited, which leads to an increase in serum concentration and a prolongation of the half-life.

When penicillin is used with acenocoumarol or warfarin, prothrombin time or other relevant coagulation parameters should be closely monitored. In addition, adjustment of the oral anticoagulant dose may be necessary.

Impact on laboratory test results

Determination of protein in urine using precipitation methods (sulfosalicylic acid, trichloroacetic acid), the Folin-Ciocalteu-Lowry method, or the Biuret method may give false-positive results. Therefore, caution should be exercised when interpreting the results of such tests in patients receiving penicillin. Protein determination using the dipstick test is not affected by penicillin;

equally, determination of uric acid using ninhydrin may lead to false-positive results;

Penicillins bind to albumin. In electrophoretic methods for determining albumin, false pseudobisalbuminemia may occur;

Non-enzymatic urine glucose tests may be falsely positive during penicillin therapy. Enzymatic urine glucose tests should be used in patients taking penicillin, as they are not affected by this interaction;

When determining 17-ketosteroids (using the Zimmerman reaction) in urine, an increase in their value may be noted.

Application features

Before starting treatment, a preliminary test for the possibility of hypersensitivity reactions to penicillins and cephalosporins should be performed. In patients with known hypersensitivity to cephalosporins, the possibility of cross-allergy should be taken into account.

Severe and sometimes fatal cases of hypersensitivity (anaphylactic reaction) have been reported in patients receiving penicillin therapy. Such reactions occur more frequently in patients with a known history of severe allergic reactions. Treatment with the drug should be discontinued and appropriate therapy instituted. Treatment of symptoms of anaphylactic reaction may be necessary, such as immediate administration of adrenaline, steroids (intravenously) and emergency treatment for respiratory failure.

The drug should be used with particular caution in the following patients:

allergic diathesis (urticaria or hay fever) or asthma (increased risk of developing hypersensitivity reactions);

severe heart disease or severe electrolyte disturbances of any other origin (note: attention should be paid to electrolyte intake in this group of patients, especially potassium intake);

renal failure;

liver damage;

epilepsy, cerebral edema or meningitis (increased risk of seizures, especially with the administration of high doses (> 20 million IU) of penicillin;

existing mononucleosis (increased risk of developing a skin rash);

in the treatment of concomitant infections in patients with acute lymphoblastic leukemia (increased risk of skin reactions);

dermatomycoses (paraallergic reactions are possible, since there is a possible common antigenicity between penicillins and metabolic products of dermatophytes).

Prolongation of prothrombin time has been reported rarely in patients receiving penicillins. Appropriate monitoring should be performed in patients receiving anticoagulants. Dosage adjustment of the anticoagulant may be necessary.

It should be borne in mind that patients with diabetes may have reduced absorption of the active substance from intramuscular depots.

When treating sexually transmitted diseases with suspected syphilis, serological tests should be performed before starting therapy and within 4 months after its completion.

Prolonged use of the drug may lead to the development of colonization with resistant microorganisms or yeasts. Superinfection is possible, which requires careful monitoring of such patients.

If severe diarrhea occurs, typical of pseudomembranous colitis (most often caused by Clostridium difficile), it is recommended to discontinue use of the drug and take appropriate measures. The use of agents that inhibit peristalsis is contraindicated.

In the treatment of Lyme disease or syphilis, a Jarisch-Herxheimer reaction may result from the bactericidal action of penicillin on the pathogens, characterized by fever, chills, and general and focal symptoms (usually 2 to 12 hours after the initial dose). Patients should be informed that these are usually transient complications of antibacterial therapy.

To suppress or alleviate the Jarisch-Herxheimer reaction, 50 mg of prednisolone or its equivalent should be administered at the first use of the drug. In patients with syphilis in the stage manifested by damage to the cardiovascular system, blood vessels and meninges, the Jarisch-Herxheimer reaction can be prevented by using prednisolone 50 mg per day or an equivalent steroid for 1-2 weeks.

For patients with severe pneumonia, empyema, sepsis, meningitis, or peritonitis who require higher serum penicillin levels, treatment with water-soluble alkaline salts of benzylpenicillin is necessary.

If neurological lesions cannot be ruled out in patients with congenital syphilis, it is necessary to use dosage forms of penicillin that achieve the highest concentration in the cerebrospinal fluid.

With intramuscular administration of the drug to infants, serious local reactions may develop, therefore intravenous administration should be preferred.

Due to possible electrolyte disturbances, benzylpenicillin should be administered slowly and no more than 10 million IU due to the possibility of epileptic seizures when administered in doses greater than 20 million IU.

Patients taking the drug in high doses for more than 5 days should have their electrolyte balance, blood count, and renal function monitored.

In severe renal dysfunction, large doses of penicillin can cause cerebral disorders, seizures, and coma.

Caution should be exercised when using the drug in infants, patients with severe cardiopathy, hypovolemia, epilepsy, and impaired renal and hepatic function.

Freshly prepared solutions for injection or infusion should be used immediately. Even when stored in a refrigerator, aqueous solutions of benzylpenicillin sodium salt decompose to form degradation products and metabolites.

1 million IU (= approximately 0.6 g) of benzylpenicillin contains 1.68 mmol of sodium; 10 million IU is equivalent to 100 ml of isotonic sodium saline solution.

Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported in patients receiving benzylpenicillin. If signs and symptoms suggestive of these reactions occur, the drug should be discontinued immediately and alternative treatment should be considered.

Use during pregnancy or breastfeeding

Benzylpenicillin crosses the placental barrier and its concentration in the fetal blood plasma 1-2 hours after administration corresponds to the concentration in the maternal serum. Available data on the use of the drug during pregnancy indicate the absence of undesirable effects on the fetus/newborn. The drug can be used during pregnancy after a careful assessment of the benefit/risk ratio.

Benzylpenicillin passes into breast milk in small amounts, therefore the risk of hypersensitivity in a breastfed child cannot be excluded. The use of the drug during this period is possible only if the expected benefit to the mother outweighs the potential risk to the child.

In infants who are partially formula-fed, breastfeeding should be discontinued if the mother is taking benzylpenicillin. Breastfeeding may be resumed 24 hours after discontinuation of treatment.

Ability to influence reaction speed when driving vehicles or other mechanisms

No negative impact on the reaction rate when driving or working with other mechanisms was observed.

Method of administration and doses

Before administration, it is necessary to collect a patient's history of drug tolerance and conduct a preliminary intradermal test for its tolerability.

Only water for injection is used to prepare the solution.

For premature and newborn infants (up to 2 weeks old), the dose interval should be at least 12 hours.

Dosage in renal impairment

In patients with severe renal impairment, single doses of the drug and the intervals between them should be established according to creatinine clearance.

Adults and adolescents

Infants from 1 month of age and children up to 12 years of age

If renal function is moderately to severely impaired (glomerular filtration rate = 10-50 ml/min/1.73 m2), the normal dose should be administered every 8-12 hours. In very severe cases of renal function impairment or renal failure (glomerular filtration rate <10 ml/min/1.73 m2), the normal dose should be administered every 12 hours.

Premature and newborn babies (up to 4 weeks old)

Patients with impaired liver function No dose reduction is required provided that renal function is not impaired.

Special dosage recommendations:

for streptococcal infections, the drug should be used for at least 10 days to prevent complications;

Bacterial endocarditis: adults should be prescribed 10-80 million IU/day intravenously in combination with aminoglycosides;

meningitis: daily doses should not exceed 20-30 million IU for adults and 12 million IU for children to prevent convulsions and Jarisch-Herxheimer reactions. In severe clinical conditions, the first dose should be spread out over time, starting with ¼ of the individually prescribed single dose, and administered slowly, carefully monitoring the patient;

Poisoning by pale toadstool: usual dose 0.5-10 million IU/kg/day;

Lyme borreliosis: 20-30 million IU per day intravenously for adults and 0.5 million IU/kg/day intravenously for children, divided into 2-3 doses, for 14 days.

The drug can also be used:

intrapleurally in doses up to 0.2 million IU (5,000 IU/ml of solvent);

intraarticularly in doses up to 0.1 million IU (25,000 IU/ml of solvent);

intralumbar in doses not exceeding 10,000-20,000 IU for adults and 8,000 IU for children aged 6-12 years, 5,000 IU for children aged 1-6 years and 2,500 IU for newborns (1–23 months).

The sterile solution (concentration not higher than 1000 IU/ml of solvent) should be warmed to body temperature and administered slowly (1 ml/min) after removal of an appropriate amount of cerebrospinal fluid. With intralumbar administration, the dose of the drug is an addition to systemic treatment, therefore the total daily dose of benzylpenicillin for systemic administration (intravenously or intramuscularly) should be reduced accordingly.

Method of application

The drug should be administered intravenously (IV) in the form of injections or short-term infusions and intramuscularly (IM).

To prepare a solution for intravenous injection, dissolve no more than 10 million IU of benzylpenicillin in 10 ml of water for injection.

When administered intramuscularly, the total volume of fluid administered should not exceed 5 ml per injection site. With repeated injections, the injection site should be changed. Higher doses should be administered intravenously by drip. Severe local reactions may occur in children with intramuscular administration, therefore it is preferable to use the intravenous route of administration.

To prepare an infusion solution, dissolve 10-20 million IU of benzylpenicillin in 100 or 200 ml of water for injection, respectively; at the indicated ratios, a solution close to isotonic is obtained.

It is not recommended to use Ringer's solution, lactate or other solutions containing sodium to prevent the development of electrolyte imbalance. The infusion should be carried out over 15-30 minutes.

Caution: Cerebral seizures may occur with rapid administration.

The usual duration of treatment is 10 to 14 days for most indications. However, the duration of treatment should be adjusted according to the severity of the infection, the susceptibility of the pathogen, and the clinical and bacteriological status of the patient. Treatment should be continued for 2 to 3 days after the disappearance of the main symptoms of the disease.

Children

Prescribe to children from birth. The drug should be used with extreme caution in children under 2 years of age.

Overdose

Symptoms of overdose largely correspond to the nature of the side effects. Gastrointestinal disorders and disturbances of water and electrolyte balance are possible. Increased neuromuscular excitability or a tendency to cerebral convulsions is possible.

Treatment: There is no specific antidote. Treatment includes hemodialysis, gastric lavage, and symptomatic therapy; special attention should be paid to water and electrolyte balance.

Side effects

Criteria for assessing the frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), isolated (≥ 1/10,000, < 1/1000), rare (< 1/10,000), including isolated reports.

Blood and lymphatic system disorders: rare - eosinophilia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia, agranulocytosis, pancytopenia. In addition, hemolytic anemia, coagulation disorders and a positive Coombs test are possible. Prolongation of bleeding time and prothrombin time have been reported.

On the part of the immune system: rare - allergic reactions: urticaria, angioedema, erythema multiforme, exfoliative dermatitis, contact dermatitis, fever, joint pain, anaphylactic or anaphylactoid reactions (asthma, thrombocytopenic purpura, gastrointestinal symptoms). Paraallergic reactions may occur in patients with dermatomycoses, as they may be a consequence of antigenicity between penicillin and metabolic products of dermatophytes. Serum sickness, Jarisch-Herxheimer reaction in combination with spirochetal infection (syphilis and tick-borne borreliosis) have been reported.

Nervous system: rare - with high-dose infusion (adults over 20 million IU), there is a particularly high risk of convulsions in patients with severe renal impairment, epilepsy, meningitis, cerebral edema or when using an extracorporeal circulation device; neurotoxic reactions, including hyperreflexia, myoclonic twitching; coma, symptoms of meningism, paresthesia. Neuropathy.

On the part of the digestive tract: infrequently - stomatitis, glossitis, black tongue, nausea, vomiting, diarrhea. If diarrhea appears during treatment, the possibility of pseudomembranous colitis should be considered, rarely - diarrhea caused by Clostridium difficile.

From the hepatobiliary system: very rarely - hepatitis, bile stasis.

Skin: pemphigoid, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).

From the kidneys and urinary system: rare - interstitial nephritis, nephropathy (with intravenous administration of doses exceeding 10 million IU), albuminuria, cylindruria and hematuria. Oliguria or anuria, as a rule, disappear within 48 hours after discontinuation of therapy. Diuresis can be restored after the use of 10% mannitol solution.

Other: reactions at the injection site; with intravenous administration, the development of phlebitis or thrombophlebitis is possible; severe local reactions with intramuscular administration in infants; prolonged use of antibiotics can lead to the development of secondary superinfections caused by resistant microorganisms; candidiasis; in the treatment of syphilis or other infectious diseases caused by spirochetes (Lyme disease, relapsing typhus), the process of bacterial lysis can cause the Jarisch-Herxheimer reaction with the following symptoms: chills, myalgia, headache, tachycardia, vasodilation with changes in blood pressure; hypersensitivity reactions (itching, laryngospasm, bronchospasm, hypotension, vascular collapse); serum sickness (including such manifestations as fever, weakness, arthralgia, abdominal pain, rash); high doses of the drug can lead to the development of congestive heart failure.

Expiration date

5 years.

Storage conditions

Store at a temperature not exceeding 25 °C.

The solution must be used immediately after preparation.

Keep out of reach of children.

Incompatibility

The powder should be diluted in water for injection.

Do not mix with other injection solutions containing cimetidine, cytarabine, chlorpromazine, dopamine, heparin, hydroxyzine, lactate, lincomycin, metaraminol, sodium bicarbonate, oxytetracycline, pentobarbital, tetracycline, sodium thiopental, vancomycin, Ringer's solution. Benzylpenicillin is incompatible in solution with vitamin B complex and ascorbic acid.

Benzylpenicillin solutions are most stable in the pH range of 6-7 (optimal pH 6.8).

Packaging

Powder in a vial. 100 vials in a cardboard box.

Vacation category

According to the recipe.

Producer

Sandoz GmbH – TechOps/Sandoz GmbH – TechOps.

Address

Biochemiestrasse 10, 6250 Kundl, Austria.